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Chronic central serotonin depletion attenuates ventilation and body temperature in young but not adult Tph2 knockout rats. J Appl Physiol (1985) 2016 May 01;120(9):1070-81

Date

02/13/2016

Pubmed ID

26869713

Pubmed Central ID

PMC4855209

DOI

10.1152/japplphysiol.01015.2015

Scopus ID

2-s2.0-84984672514 (requires institutional sign-in at Scopus site)   35 Citations

Abstract

Genetic deletion of brain serotonin (5-HT) neurons in mice leads to ventilatory deficits and increased neonatal mortality during development. However, it is unclear if the loss of the 5-HT neurons or the loss of the neurochemical 5-HT led to the observed physiologic deficits. Herein, we generated a mutant rat model with constitutive central nervous system (CNS) 5-HT depletion by mutation of the tryptophan hydroxylase 2 (Tph2) gene in dark agouti (DA(Tph2-/-)) rats. DA(Tph2-/-) rats lacked TPH immunoreactivity and brain 5-HT but retain dopa decarboxylase-expressing raphe neurons. Mutant rats were also smaller, had relatively high mortality (∼50%), and compared with controls had reduced room air ventilation and body temperatures at specific postnatal ages. In adult rats, breathing at rest and hypoxic and hypercapnic chemoreflexes were unaltered in adult male and female DA(Tph2-/-) rats. Body temperature was also maintained in adult DA(Tph2-/-) rats exposed to 4°C, indicating unaltered ventilatory and/or thermoregulatory control mechanisms. Finally, DA(Tph2-/-) rats treated with the 5-HT precursor 5-hydroxytryptophan (5-HTP) partially restored CNS 5-HT and showed increased ventilation (P < 0.05) at a developmental age when it was otherwise attenuated in the mutants. We conclude that constitutive CNS production of 5-HT is critically important to fundamental homeostatic control systems for breathing and temperature during postnatal development in the rat.

Author List

Kaplan K, Echert AE, Massat B, Puissant MM, Palygin O, Geurts AM, Hodges MR

Authors

Aron Geurts PhD Professor in the Physiology department at Medical College of Wisconsin
Matthew R. Hodges PhD Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Body Temperature
Female
Hypoxia
Male
Mutation
Neurons
Raphe Nuclei
Rats
Respiration
Serotonin
Tryptophan Hydroxylase
Ventilation